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The Chaperone FACT and Histone H2B Ubiquitination Maintain S. pombe Genome Architecture through Genic and Subtelomeric Functions.
Molecular Cell ( IF 14.5 ) Pub Date : 2019-12-11 , DOI: 10.1016/j.molcel.2019.11.016
Magdalena Murawska 1 , Tamas Schauer 2 , Atsushi Matsuda 3 , Marcus D Wilson 4 , Thomas Pysik 1 , Felix Wojcik 5 , Tom W Muir 5 , Yasushi Hiraoka 3 , Tobias Straub 2 , Andreas G Ladurner 1
Affiliation  

The histone chaperone FACT and histone H2B ubiquitination (H2Bub) facilitate RNA polymerase II (Pol II) passage through chromatin, yet it is not clear how they cooperate mechanistically. We used genomics, genetic, biochemical, and microscopic approaches to dissect their interplay in Schizosaccharomyces pombe. We show that FACT and H2Bub globally repress antisense transcripts near the 5' end of genes and inside gene bodies, respectively. The accumulation of these transcripts is accompanied by changes at genic nucleosomes and Pol II redistribution. H2Bub is required for FACT activity in genic regions. In the H2Bub mutant, FACT binding to chromatin is altered and its association with histones is stabilized, which leads to the reduction of genic nucleosomes. Interestingly, FACT depletion globally restores nucleosomes in the H2Bub mutant. Moreover, in the absence of Pob3, the FACT Spt16 subunit controls the 3' end of genes. Furthermore, FACT maintains nucleosomes in subtelomeric regions, which is crucial for their compaction.

中文翻译:

Chaperone FACT 和组蛋白 H2B 泛素化通过基因和亚端粒功能维持粟酒裂殖酵母基因组结构。

组蛋白伴侣 FACT 和组蛋白 H2B 泛素化 (H2Bub) 促进 RNA 聚合酶 II (Pol II) 通过染色质,但尚不清楚它们如何机制合作。我们使用基因组学、遗传学、生物化学和微观方法来剖析它们在粟酒裂殖酵母中的相互作用。我们表明,FACT 和 H2Bub 分别全局抑制基因 5' 端附近和基因体内部的反义转录本。这些转录本的积累伴随着基因核小体和 Pol II 重新分布的变化。H2Bub 是基因区域 FACT 活性所必需的。在 H2Bub 突变体中,FACT 与染色质的结合发生改变,并且其与组蛋白的关联稳定,从而导致基因核小体的减少。有趣的是,FACT 耗尽可全局恢复 H2Bub 突变体中的核小体。此外,在缺乏 Pob3 的情况下,FACT Spt16 亚基控制基因的 3' 末端。此外,FACT 将核小体维持在亚端粒区域,这对于核小体的压缩至关重要。
更新日期:2019-12-11
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